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Atazanavir (Reyataz; ATV) is a well-tolerated protease inhibitor (PI) that is indicated as a once-daily treatment for HIV infections. These features of ATV, combined with its virologic potency, make it particularly desirable for the treatment of HIV-infected pediatric patients. The objective of this study was to use a model-based approach to recommend body weight-based ATV capsule doses for pediatric patients. ATV concentration-time data from three adult studies and one pediatric study were described by a C0-delinked one-compartment model to guard against introducing bias in pharmacokinetic (PK) parameter estimates due to the potential nonadherence in outpatient studies. The apparent clearance (CL/F) and apparent volume of distribution (V/F) were determined to increase with body weight, and CL/F was 40.9% lower in patients receiving ATV comedication with ritonavir (RTV). The relative bioavailability (Frel) of ATV was 132% higher with RTV comedication and was 35.5% lower for the ATV powder formulation than the capsule formulation. Model-based simulations were used to recommend weight-based ATV capsule doses of 150 to 300 mg boosted with 100 mg RTV for pediatric patients weighing ≥15 kg, such that the exposures in these patients are similar to those obtained in HIV-infected adults treated with the recommended ATV/RTV dose of 300/100 mg.
There is an unmet medical need for the development of potent, safe, well-tolerated, and simplified once-a-day therapies for children infected with HIV. Virologic failure and long-term drug-related toxicities have become increasingly common in children, and thus there is a need for drugs that offer improved tolerability and resistance to viral mutations, with convenient dosing schedules. Atazanavir (Reyataz; ATV) is an azapeptide protease inhibitor (PI) that is approved in the United States for the treatment of HIV-infected adults and children in combination with other antiretrovirals (3). The safety profile of ATV is notable for causing fewer perturbations in lipids and less gastrointestinal intolerance than the other PIs. In adult and pediatric patients, the most common side effect of ATV is indirect bilirubin elevation due to inhibition of the UDP-glucuronil transferase enzyme, which is usually well tolerated and does not lead to treatment discontinuation (9). Additionally, ATV combines virologic potency with a high barrier for development of cross-resistance to other PIs (16). On these grounds, ATV represents an ideal PI for the treatment of HIV-infected pediatric patients.
The safety, efficacy, and pharmacokinetics (PK) of ATV in HIV-infected pediatric patients, with or without ritonavir (RTV), were studied in trial PACTG1020 (ClinicalTrials.gov identifier NCT00006604). The ATV doses in this study were body surface area (BSA) normalized and adjusted to target exposures and safety criteria prespecified in the protocol. A BSA-based ATV dose of 205 mg/m2 met the prespecified criteria for patients older than 6 years taking ATV capsules with RTV. However, given the available ATV capsule dose strengths (100, 150, 200, and 300 mg), it is not possible to administer the exact mg dose equivalent to the BSA dose. The BSA dose was converted to the recommended body weight-tiered ATV pediatric doses in the U.S. labeling requirements. This report describes the analyses performed to further optimize the body weight-based pediatric ATV doses and to obtain approval of these doses in the European Union.
Conventional approaches to dose selection for pediatric patients have utilized size-related allometric scaling, as suggested for physiological processes across species of different sizes (1, 11). These approaches assume PK parameters to be a function of the allometric exponent of body weight, without appreciation of drug-specific PK or PK/pharmacodynamic (PD) data that are available for the adult population studied previously. Regulatory authorities, in particular the European Medicines Agency (EMA) and the U.S. FDA, have advocated model-based pediatric drug development, which offers the advantages of integrating adult and pediatric data or data from different pediatric age groups to support the use of a previously approved drug in a new target patient population (8, 19). Numerous scientific publications have provided successful examples of the added value of modeling and simulation (M&S) in pediatric drug development (5, 12, 13).
In this study, we utilized M&S as a tool to optimize the ATV capsule doses for pediatric patients by integrating available pediatric and adult data. Steady-state ATV PK data from three adult studies and one pediatric study were pooled and used to develop a population PK model. Model-based simulation was then applied to determine body weight-based ATV/RTV doses for pediatric HIV patients 6 years and older that produce ATV exposures similar to those known to be efficacious in HIV-infected adults.
Data from 4 clinical studies (3 adult and 1 pediatric) were included in the analysis. A summary of the study designs is shown in Table 1.
The pediatric study PACTG1020 investigated the PK, safety, and tolerability of ATV in antiretroviral treatment (ART)-naïve and -experienced HIV-infected infants, children, and adolescents. The eligible subjects were assigned to treatment groups that were stratified by age, ATV formulation, and RTV comedication (yes/no), as shown in Table 2. The starting ATV dose for all groups was 310 mg/m2 once a day (QD). The RTV-boosted groups also received RTV at 100 mg/m2 QD (up to 100 mg QD for liquid or a 100-mg capsule QD). ATV doses were increased or decreased based on prespecified ATV PK exposure targets and safety criteria. Intensive PK samples collected over a 24-h period from 176 patients at weeks 1 and 56 and 2 weeks after the initiation of ATV dose adjustments were included in this analysis.
The plasma concentration of ATV was determined using a validated high-performance liquid chromatography-tandem mass spectrometry method (17). A total of 3,939 ATV concentrations were included in the analysis data set, including 620 from the adult studies and 3,319 from the pediatric study. Summary statistics of the patient characteristics are listed in Table 3.
The PK data from adult and pediatric patients were pooled and analyzed by a nonlinear mixed-effects (population PK) model. The population PK analysis was performed using first-order conditional estimation (FOCE) as implemented in NONMEM software (version VI; Icon Development Solutions, Ellicott City, MD). Postprocessing of NONMEM output was performed using S-Plus (version 7.0 for Linux; Tibco Software Inc., Palo Alto, CA).
ATV pharmacokinetics was described by a C0-delinked one-compartment linear model with first-order absorption (10). The ATV structural model was parameterized in terms of first-order absorption rate (ka), elimination rate (ke), apparent volume of distribution (V/F), and relative bioavailability (Frel). A parameter to describe the predose concentration (C0) was estimated as a separate term in the model to guard against introducing bias in the compartmental PK parameters due to nonadherence (10). The ATV plasma concentration (C) at time t following an ATV dose (D) was described using the following expression:
The random-effects model includes interindividual variability (IIV) and interoccasion variability (IOV) models, which are specified by the log-normal random-effects model given by the following equation:
where θij is the value of a compartmental model parameter for the ith individual at the jth occasion, θTV is the typical value of the model parameter, ηi denotes the interindividual random effect accounting for the ith individual's deviation from the typical value, and κij denotes the interoccasion random effect accounting for the ith individual's deviation at the jth occasion. The ηi and κij values are assumed to be independent, with a mean of zero and covariance matrices denoted ΩIIV and ΩIOV, respectively.
Residual variability was described by the following log-normal residual error model:
where Yij is the observed concentration for the ith individual at time tj, Cij is the corresponding predicted concentration based on the PK model, and εij denotes the intraindividual (residual) random effect, which is assumed to have a mean of zero and a variance of σ2.
The covariates of interest were selected based on clinical and pharmacological judgment and were incorporated into the full model regardless of statistical significance. The analysis assessed the effects of several intrinsic and extrinsic covariates on ATV PK. The intrinsic covariates included body weight, age, sex, race, and ART-naïve or -experienced status, and the extrinsic covariates included formulation, RTV comedication, and study region. The covariate effects on apparent clearance (CL/F), V/F, ka, and Frel were investigated. The relationship between continuous covariates (xij) and the typical value of the PK parameters (θTV,ij) was described by a power model as follows:
where θREF and θx are the fixed-effects parameters and xREF is a reference value of the covariate xij. In the context of this analysis, the reference values for age and body weight are 18 years and 70 kg.
The relationship between categorical covariates (xij) and the typical value of the PK parameters (θTV,ij) was modeled as follows:
where θREF and θx are the fixed-effects parameters and xij is the indicator variable, which is equal to 1 or 0 depending on the category of the covariates.
The covariate model was parameterized by assuming multiplicative effects for both the continuous and categorical covariates. Wald's approximation method (WAM) was used to identify a final parsimonious model relative to the full covariate model (14). To further evaluate the degree of parsimony of the final model, forward selection followed by backward elimination was performed on the final model. A change of objective function value (OFV) equal to the logarithm of the number of observations was set as a cutoff criterion for the inclusion and exclusion of the covariates to be consistent with Schwarz's Bayesian criterion (SBC), employed by the WAM procedure.
The final population PK model was evaluated using a visual predictive check (VPC) and posterior predictive check (PPC). VPC was conducted by simulating 500 data sets, using the final model population parameter estimates. The 10th, 50th, and 90th percentiles (80% VPC interval) of the simulated data were constructed and superimposed on the observed data in the original analysis data set. The percentage of observed concentration data outside the 80% VPC interval was calculated to assess the consistency of observed and model-predicted concentration values.
PPC was conducted by assuming that the final model parameter estimates (θ, Ω, and Σ) followed a multivariate normal distribution, with the mean vector set to the population parameter estimates and the covariance matrix set to the variance-covariance matrix of the estimates (20). One thousand simulated data sets conditioned on the study designs, dose regimens, and covariates in the observed data set were generated by using 1,000 sets of population parameter values sampled from the multivariate normal distribution. For each simulated data set as well as the observed data set, the ATV trough concentration (Cmin), peak concentration (Cmax), and area under the concentration-time curve (AUC) were calculated for each simulated subject and used as PPC statistics. The observed statistics were compared to the median and the 5th and 95th percentiles of the 1,000 simulated statistics.
Model-based simulations were conducted to evaluate a comprehensive set of weight-based dosing scenarios for pediatric patients weighing ≥15 kg given ATV capsule doses in combination with RTV. The simulation was not conducted for pediatric patients weighing <15 kg due to insufficient data on efficacy and safety. The final population PK model was used to simulate steady-state ATV concentration-time curves for 10,000 hypothetical subjects for each dosing scenario. Individual body weights for 10,000 hypothetical subjects were sampled from a uniform distribution within each weight group. Values for Cmin, Cmax, and AUC were calculated for each of the simulated steady-state ATV concentration-time profiles. These results were subsequently summarized by calculating the geometric mean (GM) across the 10,000 simulated subjects.
A bridging strategy was adopted to determine pediatric doses that produced exposures determined to be safe and efficacious in adults. Weight-based pediatric ATV capsule doses were identified by determining the doses that produced summary steady-state exposures (Cmin, Cmax, and AUC) that were similar to target exposures achieved in HIV-infected adults receiving the recommended adult dose (ATV/RTV at 300/100 mg QD). The similarity criteria for exposures in pediatric and adult patients were defined as follows: GM of pediatric Cmin of >75% of GM of adult Cmin, GM of pediatric Cmax of <150% of GM of adult Cmax, and GM of pediatric AUC within 80 to 125% of GM of adult AUC.
In addition, we determined the percentage of pediatric subjects attaining exposures within the 10th and 90th percentiles of the adult exposures produced by the adult recommended dose. A percentage of >75% in conjunction with exposure similarity was deemed to be appropriate for proposing weight-based ATV pediatric doses.
The base population PK model describing steady-state ATV concentration-time profiles was determined to be a C0-delinked one-compartment model with delayed first-order absorption and first-order elimination. This modeling approach has been shown to perform better than the conventional method (which assumes 100% treatment adherence), based on the bias and imprecision of parameter estimates and the power and type I error in the likelihood ratio test for covariate effects (10, 18). RTV coadministration was included as a fixed effect in C0 in view of the higher ATV trough concentration with an ATV/RTV regimen than with ATV alone. Under full adherence, C0 is expected to be dose proportional; hence, it was of interest to assess whether C0 was dose proportional across the wide range of ATV doses investigated in the pediatric study (48 to 1,200 mg QD). The relationship between ATV dose and C0 was investigated by incorporating a proportional dose effect on C0 for ATV and ATV/RTV regimens. The OFVs were compared to that for the model with no dose effects on C0. The incorporation of the ATV dose effect resulted in a large reduction in OFV, by 84 points, and comparison of OFVs for the ATV dose effect revealed that the reduction can be explained primarily by the dose effect on C0 for the ATV/RTV regimen.
The random-effects model incorporates IIV effects on ka, ke, and V/F and IOV effects on ke, Frel, and C0. The IOV effect on C0 was modeled as having both a PK component and a nonadherence component. The PK-related IOV component on C0 was likely due to IOV on Frel, so the same variance component was included on both C0 and Frel. Residual variability was modeled using the log-transform error model as shown in Equation 3. Separate residual variance components were included for ATV alone and ATV/RTV, to account for the differences in residual variability between these two treatment regimens.
Models that included all possible combinations of covariate parameters in the full model were evaluated by the WAM procedure. The top 15 WAM-ranked models, in order of decreasing SBC, were then fit in NONMEM. The model with the highest actual SBC based on the NONMEM runs corresponded to the top WAM-ranked model, but the correlation coefficient of WAM- and NONMEM-based SBCs was low (r = 0.157). Therefore, further ad hoc NONMEM-based model evaluations were undertaken to confirm the selection of the final model. A combination of forward selection and backward elimination was performed, starting with the top WAM-ranked model, using 8.279 [log(n) = log(3,939)] as the cutoff of ΔOFV for inclusion and exclusion of a single covariate parameter. The ad hoc stepwise runs did not result in the inclusion of additional covariates or the removal of existing covariates from the model, suggesting that the top WAM-ranked model was parsimonious, and therefore this model was selected as the final model.
The final model contained the following covariate effects: age effect on ka; body weight effect on V/F; region (Africa), body weight, sex, and RTV comedication effects on CL/F; and formulation and RTV comedication effects on Frel. All covariates had effect magnitudes outside ±20% of reference covariate values, except for the effects of region (Africa) and sex on CL/F (Fig. 1 and and2).2). The final model parameter estimates are provided in Table 4. The negative exponent for the age effect on ka indicates that infants and younger children had an increased rate of absorption that resulted in a higher Cmax than that for adolescents and adults. The CL/F for a male in North America/Europe with a body weight of 70 kg receiving ATV alone was 34.6 liters/h, and the V/F for a subject with a body weight of 70 kg was 266 liters. The inclusion of an RTV comedication effect on C0, CL/F, and Frel described the substantially higher ATV exposures for patients receiving ATV/RTV than those for patients receiving ATV alone, which is consistent with the mechanism of drug interaction between ATV and RTV (15). The PK estimates of our analysis showed some discrepancy with previously reported data (CL/F of 12.9 liters/h for ATV alone and 7.0 liters/h for ATV/RTV, V/F of 88.3 liters, and ka of 0.405 h−1) (7). However, the ATV elimination half-lives (5.3 h for ATV alone and 9.0 h for ATV/RTV) were in accordance with published data (4.6 h for ATV alone and 8.8 h for ATV/RTV) (7). Finally, the model predicted an approximately 35.5% reduction in bioavailability for the powder formulation relative to the capsule formulation.
The predictive performance of the final model was evaluated by VPC and PPC. The VPC plot (see Fig. S1 in the supplemental material) demonstrated that model predictions were largely in agreement with the observed data. The percentages of observations outside the 80% VPC intervals were close to the nominal value of 20%, with the exception of a few age groups that had percentages of <10% (see Table S1).
Figure 3 shows the final model posterior predictive distribution (medians with 5th and 95th percentiles) of GMs for Cmin, Cmax, and AUC overlaid with the observed GMs for ATV at week 1 in pediatric and adult subjects. The PPC of GMs (and standard deviations) of Cmin, Cmax, and AUC provided an evaluation of the model-predicted central tendency (and variability) of these exposure measures. The PPC was stratified by the 8 pediatric age/treatment groups in PACTG1020, and groups 1 and 5 were further stratified into younger (3 months to 1 year) and older (1 to 2 years) infants to assess the adequacy of the model for predictions of exposures in younger infants. Two additional stratification groups, for adults receiving ATV alone or ATV/RTV, were also included. The observed GMs for Cmin, Cmax, and AUC generally fell within the 5th and 95th percentiles of the predictive distribution for the final model across the pediatric age groups as well as the adult groups, with the exception of Cmin for the younger infants in group 1 and AUC for the younger infants in group 5. Group 1 had only one subject younger than 1 year, resulting in less precision in the prediction than that for the other groups. The GM of observed AUC in group 5 was calculated from 6 subjects and is about 20% less than the 5th percentile limit (16.3 versus 20.7 μgh/ml). The observed GMs for Cmin, Cmax, and AUC at week 56 generally fell within the 5th and 95th percentiles of the predictive distribution (see Fig. S2 in the supplemental material).
A series of ad hoc simulations were conducted to evaluate comprehensive dosing scenarios for RTV-boosted ATV capsules in HIV-infected pediatric patients in selected weight groups (≥15 kg, with 5-kg increments). The proposed weight-based pediatric ATV/RTV capsule doses are presented in Table 5. The body weight ranges in Table 5 were obtained by collapsing the weight ranges that had the same doses meeting the similarity criteria. Figure 4 presents comparisons of pediatric GMs with target values for each of the evaluated weight-based dose regimens. ATV/RTV at 200/100 mg is predicted to produce a sufficiently high Cmin for pediatric patients weighing <40 kg; however, this dose produces an excessively high Cmax and AUC for patients weighing <20 kg. Hence, ATV/RTV at 150/100 mg is proposed for children in the 15 to <20 kg weight group. We noted that ATV/RTV at 250/100 mg appeared to be a more appropriate dose than ATV/RTV at 200/100 mg for the 35 to <40 kg weight group, as it satisfied the similarity criteria while attaining higher exposures than ATV/RTV at 200/100 mg. However, this dose is not recommended because the 250 mg ATV dosage strength requires the use of two different capsule strengths (100 mg and 150 mg) and is therefore prone to dosing errors. Pediatric patients weighing ≥40 kg are recommended to take the adult, label-recommended dose. The percentage of pediatric subjects with Cmin, Cmax, and AUC values within the 10th and 90th percentiles of the adult values is either higher than or close to 75% for all the proposed ATV capsule doses (Table 5).
The present study illustrates the optimization of ATV/RTV capsule dose regimens for pediatric patients by utilizing M&S to bridge adult and pediatric data. The proposed ATV doses listed in Table 5 were recently approved by the European Union for use in HIV-infected pediatric patients of 6 years and older (4). These doses are predicted to achieve exposures in pediatric patients similar to those observed in adult patients receiving the recommended ATV/RTV dosing regimen (ATV/RTV at 300/100 mg once daily) that has been shown to be effective and safe. The extrapolation of efficacy from adults to pediatric patients based on similar systemic exposures was justified according to the International Conference on Harmonization (ICH) E11 guideline, in recognition that adults and children are similar in HIV pathophysiology and efficacy endpoint for drug treatment (19).
The final population PK model determined the effect magnitudes of several extrinsic and intrinsic factors on ATV PK parameters and provided adequate predictive performance of the key measures of ATV exposure (Cmin, Cmax, and AUC) that were used to evaluate and inform the pediatric dose recommendations. The population PK modeling approach (C0-delinked model) accounts for a potential lack of adherence to drug dosing recommendations by disassociating the predose concentration (which could be impacted by a lack of adherence to prior doses) from the estimation of compartmental PK model parameters. The C0-delinked model isolates the variation in exposures due to nonadherence to the C0 parameter, thereby allowing for more accurate estimation of the compartmental PK parameters (i.e., ka, V/F, and CL/F) following the known dosing time and amount of the most recent dose recorded in the clinic. Essentially, variation in C0 can be thought of as a parameter that accounts for nonadherence without requiring any imputation or additional assumptions regarding the unknown dosing history prior to the predose sample. The extent of nonadherence, quantified as the ratio of C0 under nonadherence versus full adherence, was assessed for typical individuals (body weights of 17.5, 30, and 55 kg) given the proposed, weight-based ATV/RTV capsule doses (150, 200, and 300 mg ATV, respectively, boosted with 100 mg RTV). C0 values under nonadherence were estimated to be 336, 448, and 672 ng/ml, respectively, and the corresponding C0 ratios were 65.8, 83.8, and 110%. The results suggest that higher ATV exposures translate to improved patient adherence.
To optimally balance the benefit and risk, ATV capsule dose selection for pediatric patients was targeted to achieve a GM AUC within 80 to 125% of the GM AUC in adults, while keeping the GM Cmin at >500 ng/ml (approximately 75% of the adult GM Cmin) and the GM Cmax at <6,230 ng/ml (150% of the adult GM Cmax). The determination of target exposures was supported by the efficacy and safety data observed in adult ATV clinical trials. Exposure-response analysis of data from adult studies AI424-089 and AI424-138 (ClinicalTrials.gov identifier NCT00272779) suggested that patients who achieved a Cmin of >130 ng/ml were predicted to have a >90% probability of achieving an HIV RNA reduction to <400 copies/ml and a >75% probability of achieving an HIV RNA reduction to <50 copies/ml at week 48 (2, 21). The selected target for the ATV GM Cmin (500 ng/ml) is anticipated to result in ~90% of pediatric patients achieving a Cmin of >130 ng/ml at the proposed ATV doses. With regard to safety, it was found that Cmax-dependent asymptomatic PR prolongation was more frequent in pediatric patients than in adults. Pediatric subjects who reached a Cmax of 7,000 ng/ml or above may present with PR prolongation, mostly borderline, at higher rates than subjects with a lower Cmax (42% versus 14% of 101 pediatric subjects). Given that the PR prolongations were asymptomatic, even in pediatric subjects with Cmax values as high as 20,000 ng/ml, the ATV GM Cmax of <150% of the adult value was determined as the target for Cmax which corresponds to ~90% of pediatric patients having a Cmax of <16,000 ng/ml at the proposed ATV doses. Since the peak-to-trough concentration ratios in pediatric patients are much more pronounced than they are in adults, the higher Cmax values in pediatric patients are inevitable in order to maintain an adequate Cmin to support efficacy. The proposed ATV pediatric doses strike a balance between Cmin and Cmax exposures so as to achieve an AUC similar to that in adults.
ATV capsule doses of 150 to 300 mg boosted with 100 mg RTV were recommended for ART-naïve or -experienced patients weighing ≥15 kg. The proposed weight-based ATV capsule doses were compared with the protocol-specified BSA-based dose (205 mg/m2) (3) that was administered in the PACTG1020 pediatric study. The results indicated that these weight-tiered ATV doses were similar to BSA-based doses except for the weight group of individuals weighing ≥40 kg, where the BSA-based dose was higher than the weight-based dose (data not shown). This is related to the fact that the patients in the PACTG1020 study were allowed to receive ATV doses higher than the label-approved 300 mg (with RTV boosting), while the weight-based doses proposed from model-based analysis were capped at the 300 mg adult dose. In addition, the model-based ATV dose recommendations were compared with the ATV pediatric doses currently approved in the United States and some other countries. The ATV dose regimens proposed by this model-based approach have the following advantages: (i) uniform dose recommendations for ART-naïve and -experienced patients; (ii) recommendation of an ATV capsule dose for ART-experienced patients weighing as little as 15 kg (according to the CDC growth chart [6], the median body weight for children at age 6 years who are able to swallow capsules is approximately 20 kg); and (iii) elimination of potential dosing errors resulting from the 250-mg dose, which requires the use of ATV capsules at two different strengths.
The RTV doses administered in the PACTG1020 study ranged from 26 mg to 100 mg. An ad hoc analysis was conducted to investigate whether the RTV dose explained additional variation in CL/F beyond the covariate-CL/F relationships determined in the final model (data not shown). A CL/F submodel with the covariate effects of body weight, RTV comedication (dichotomous effect due to the presence or absence of RTV), region (African), and sex was expanded to include the RTV dose effect. The submodel was fit to the individual post hoc CL/F estimates. The change in OFV (ΔOFV = 0.118) between the submodels with and without the RTV dose effect suggested that RTV dose explained little additional variation relative to the dichotomous RTV comedication effect after adjusting for the other covariate effects that were included in the final model. In the context of this analysis, we concluded that there were insufficient data to substantiate the identification of the optimal RTV dose for each weight group. As a result, the protocol-adopted RTV regimen (100 mg RTV capsule) was proposed in combination with ATV capsules for pediatric patients.
In conclusion, the population PK model developed in this analysis quantified the magnitudes of covariate effects on ATV PK and quantitatively described ATV PK in adult and pediatric patients. The use of model-based simulation in conjunction with the PK bridging strategy enabled optimization of ATV dosing regimens for pediatric patients. Future work will apply this modeling framework to the ATV powder formulation, which is currently being evaluated in HIV-infected pediatric patients younger than 6 years of age.
We thank all the pediatric patients and their families for participation in the PACTG1020 pediatric study. We acknowledge Jennifer J. Kiser, Richard M. Rutstein, Pearl Samson, Bobbie Graham, Grace Aldrovandi, Lynne M. Mofenson, Elizabeth Smith, Courtney V. Fletcher, and the PACTG1020 study team for providing data.
This analysis was sponsored by Bristol-Myers Squibb.
Kenneth G. Kowalski was a paid consultant to Bristol-Myers Squibb.
†Supplemental material for this article may be found at http://aac.asm.org/.
Published ahead of print on 19 September 2011.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Grace Coddington, Anna Wintour — And Kanye?
It's no secret that we're mildly obsessed with Grace Coddington. And, we consider any encounter with the creative genius at Fashion Week to be one of the best days, ever. So, while we always kind of have our fingers crossed that we'll spot that unmistakable, gorgeous red hair at a designer's show, we're completely jealous of Laura Brown, the Harper's Bazaar Executive Editor who caught a glimpse of Coddington somewhere totally unexpected: the Kanye concert.
What's more is that it looks like she had Anna Wintour with her. What does this all mean? Have Coddington and Wintour been Kanye fans for a while, and no one ever thought to ask them? Is having fashion's power players at his concert finally an endorsement for Kanye's designer dreams? Or, based on their proximity to the sound and lighting station, were the pair simply freelancing as creative directors for the Yeezus tour stop in Brooklyn? We defer to you, dear reader. (Huff Post)
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December 13, 2011
As catchy as it is predictable, Cometas por el Cielo is one of those records that are too perfect for their own good. The band plies its usual wares on its sixth album, offering high-quality pop/rock that's really too sweet and airy to be called power pop, though that's where its roots are (as shown by the fuzz-laden opener, the one exception). Angelic singing by Leire Martínez forms a gentle contrast with the guitar-driven music, but the distortion is barely audible, and bouncy beats (sometimes electronic) and romantic melodies smooth out all the rough edges. They also go heavy on ballads, complete with pianos and strings, which really put Martínez 's voice in the spotlight, though all traces of rock are absent from those numbers. On the whole, La Oreja de Van Gogh are tapping the same well of inspiration as all skilled guitar popsters, down to Avril Lavigne -- it's basically '80s pop, melody-driven and shamelessly tugging at the heartstrings just the way Bangles and Bryan Adams used to do in their respective heydays. In Oreja 's case, however, the result is more similar to immaculate Japanese pop than Lavigne , with technical flawlessness prized over identity. It's just too mainstream, in the sense that these songs could have been recorded by anyone from Eros Ramazzotti (well, if he were a girl, or sang duets with one) to Kanagawa prefecture's Ikimono Gakari , and no one would have batted an eyelid. Cometas por el Cielo is a wonderful pick for those looking for sleek pop/rock done the right way, but it's telling that its biggest claim to individuality is the language of the lyrics. ~ Alexey Eremenko, Rovi
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Katie Price sues ex-husband Peter Andre
Katie Price is taking legal action against her ex-husband Peter Andre, almost three years after the couple divorced.
The model has also included her ex-manager Claire Powell, who runs management company Can Associates and her former friend Jamelah Asmar in that action.
Representatives for Katie confirmed she is suing them through the High Court.
She's accusing them of breach of confidence.
They would not confirm how much she was seeking in damages.
A spokesman for Katie Price told Newsbeat: "Kate is having to continue her claim against her ex-husband; ex-manager and ex-friend for breach of confidence.
False smears
"The pleadings in that action speak for themselves and Kate has no comment to add."
According to newspaper reports, the former glamour model is accusing the three defendants of being responsible for a smear campaign against her.
The 34-year-old says one of her ex-employees was asked to gather false smears about her personal life after she split from Peter Andre.
The result, she says, was an email which claimed she was about to have an affair with her riding instructor, Andrew Gould.
There's currently no word from Peter Andre, Claire Powell or Jamelah Asmar on the matter.
Last year, Katie had to pay damages and apologise to Peter Andre over claims he'd cheated on her and wasn't genuine in his feelings with her son Harvey, who has a different father.
Katie is set to marry for a third time, to Argentine model Leandro Penna, but no date has been confirmed.


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- Book 1 of 3 in Briarwood Academy (3 Book Series)
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And who wouldn't lust after Leo Tate? He's a tattooed, hot musician with icy blue eyes and effortless sex appeal. He's guarded but kind and giving. He was intent on avoiding a serious relationship, but he became jealous and possessive whenever she's near. The more he fought his feelings for Nora, the more he can't resist her.
Leo and Nora had amazing chemistry together. Their witty banter and sizzling attraction to each other ignited the pages on fire. My favorite moment occured between them when she locked them into the music room. That uninhibited masturbation scene was deliciously hot, hot, hot...And then she dropped a bombshell on him...And then her dirty secret. My mouth hung open, and I was simply wowed!
"Spread your legs, Leo. Just shut up and do it, okay? Do this one thing for me. Let me see you. All of you." ~ Nora Blakely
The secondary characters really added to Leo and Nora's story. There were plenty of villians: Nora's mom; her half-brother, Finn; the bully at school, Emma Eason; and Leo's friend-with-benefits, Tiffani (with an i). Then, there was Teddy, the autistic musical savant, who was completely adorable and loveable. And Drew Mansfield and Cuba 'Hollywood' Hudson included additional heat and spice into the mix.
But for me, Sebastian Tate stole the show and my heart! His relationships with Leo and Nora were completely endearing. He was sweet and charming, yet edgy too.Read more ›
Nora is in her last year of high school at Briarcrest Academy and she is what you consider a genius with a high IQ. She is tall and thin, plays the piano, has won several spelling bees and even a few pageants. Her mother made sure she was the epitome of perfection in every way. Sadly her mother failed miserably at what a mother is supposed to do for their child and I hated her for that.
But, Nora has secrets and she has lost herself quite possibly gone mad. She is drinking and partying. She has also made this list of bad things she wants to do and I was intrigued. I wanted to know her secrets.
Her mother and father are always gone and Nora is left alone. She also has a brother Finn who she did not have the best relationship with and I just new in the beginning he was trouble.
Nora is practically on her own but deep down she is so lonely and it made me so very sad! She had her quirks like we all do and what really tripped me out was her thing for words! She also people watches and quite frankly I was enamored by her.
After a particular episode at school, that is witnessed by all, we are introduced to Leo Tate and his younger brother Sebastian. They are new in town and Sebastian will be going to Briarcrest Academy. Leo, however is older, about 25, and Sebastian's guardian since their parents were killed.Read more ›
Nora Blakely appears to be the perfect girl. Perfect looks, top of her class, talented and parents who are extremely successful. She wants for nothing...except to escape it all! Leo Tate has relocated to Highland Park, Texas with his younger brother and has enrolled him in Briarcrest Academy where Nora is speaking at the registration and open house night as the student body representative. Seven little words, two of them cuss words, change it all!
The connection between Leo and Nora from the first moment their eyes meet is explosive! Leo is the guardian for Sebastian and is opening a new gym in Highland Park. Nora's life hasn't been as perfect as it seems and she is ready to take control which includes making several bad choices. One of them leads her to Leo and Sebastian who happen to live across the street from Nora's aunts bakery. Trying to get a handle on Nora is a challenge in and of itself, let alone dealing with her heart. She is deeply broken and Leo is determined to fix her, but it won't be easy. The problem with trying to fix someone is that you risk opening your heart...a heart that has its own scars. The struggle between Leo and Nora is intense, emotional and feels so real. The secondary characters in the book are amazing and I fell in love with a few and deeply despised others! Those relationships and interactions help to crack through both of their hardened hearts and open their eyes to what is right in front of them...one another!
The intensity of Leo and Nora's love is beautiful and heartbreaking. The steam factor of this book is off the charts sizzling!! This is the first book in the series and it is not a cliffhanger, you will however, see them in the other books. Leo and Nora have a special place in my heart and always will...
Most Recent Customer Reviews
There is some dark subject matter in this book. But it is also filled with HOPE!!
I enjoyed the storyline and the characters created for this book. Read more
This book was awful - I have no idea how it got such a positive rating. There are lots and lots of typos - I am not talking about simple misspellings, but entire words missing. Read morePublished 3 days ago by Jennifer J Brady
Once upon a star, very bad things, can turn into very good things. Nora lives a truly horrendous existence. Read morePublished 3 days ago by Melinda Adams
Holy Moly what a book! Wow! I'm not sure how to review it because it wasn't anything I expected. I read the first few chapters as a bonus feature in the book Dirty English. Read morePublished 10 days ago by ColetteT
Easy read and very addicting story, I didn't want to put the book down.Published 11 days ago by Angela Accavitti
I love the BA books and this is one of my favorites. Nora was the spoilt rich kid everyone thought she was. Read morePublished 11 days ago by Karie Gibson
This is a book that grabs you from the first chapter and keeps you in a chokehold for the entire story.
We meet Nora at one of the lowest points of her young life. Read more
Quick read. Story line was somewhat believable, as I live in the greater Dallas area. Lead girl was likeable so was lead guy, brother was funnier however. So was supporting friend. Read morePublished 14 days ago by Jade Ranes
I loved this book and the characters. Some of the quotations and sentences are fantastic. For example: "If love is the answer, then I'm changing the question. Read morePublished 14 days ago by Jeff
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Home-Based Intervention Aims to Curb Childhood Tooth Decay and Obesity in the Bronx
Living Longer Associated with Living Healthier, Study of Centenarians Finds
Einstein Education Researcher Named 2016 Macy Faculty Scholar
Concussion Outcome Predicted Using Advanced Imaging
Obese Young Adults Unaware of Kidney Disease Risk, Study Finds
Einstein Celebrates Its 58th Commencement
Dr. Kamran Khodakhah Named Chair of Neuroscience at Albert Einstein College of Medicine
May 11, 2007 - (BRONX, NY) - Jed M. Shivers has been appointed Associate Dean for Finance and Administration at the Albert Einstein College of Medicine of Yeshiva University, it was announced by Allen M. Spiegel, M.D., The Marilyn and Stanley M. Katz Dean of the medical school.
Mr. Shivers succeeds Associate Dean Emanuel Genn, who is retiring after 35 years of service to Einstein.
Mr. Shivers brings especially broad and diverse experience at a number of the nation's leading medical institutions to his new role at Einstein. Most recently he was at the University of California, San Francisco, where he oversaw all financial activities of the institution and was also Senior Associate Dean for Clinical Programs. Prior to that, he was at Yale University School of Medicine where he first served as administrator for the Departments of Pediatrics and Surgery and later as the medical school's Chief Administrative and Financial Officer. Earlier, Mr. Shivers was administrator of the Department of Medicine at Stanford University School of Medicine.
Mr. Shivers earned his B.A. degree in the natural sciences from John Hopkins University in 1978 and an M.B.A. degree from the University of Connecticut School of Business in 1980.


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Rarely do we find a "literary love story," the genre itself seems to have faded into classics. For those of us who have lost hope of their revitalization, look no further than Tom McNeal's "To Be Sung Underwater." His second novel delivers with intellectually capable characters that do not merely fall in love, but question love itself in all its manifestations.
Judith and Willy had one summer together. Yet their languid days spent swimming in secret lakes and the cool nights picnicking under the stars still hang suspended in the backdrop of Judy's life years later. As for Willy, those few days with Judith have proved to be the piéce de résistance of his life. Circumstance and destiny, although often at odds, work together to make a mess of their plans, condemning them to separate fates.
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23rd Annual Potawatomi Trails Pow Wow
The Potawatomi Trails Pow-Wow is the only event of its kind in this area. This celebration of the Native-American heritage heightens the awareness of the history, traditions and customs of the heritage. Specific activities include demonstrations, music and dance presentations, educational sessions and a trader area.
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Virginia Dressage Association CHARLOTTESVILLE Chapter
New News!
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All Forms, including USEF Vaccine reporting
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VADA-CH Isabel F de Szinay Memorial Dressage Show
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I am grateful to Professor Chris Pickvance and the four IJURR referees for their comments on earlier drafts of this article. Any remaining errors are the responsibility of the author.
Extending the Resource-Based Approach to Livelihoods: An Urban Application to Turkish Gecekondu Households
Version of Record online: 19 FEB 2013
DOI: 10.1111/j.1468-2427.2013.01205.x
© 2013 Urban Research Publications Limited
International Journal of Urban and Regional Research
Volume 37, Issue 2, pages 769–789, March 2013
Additional Information
How to Cite
Eroğlu, Ş. (2013), Extending the Resource-Based Approach to Livelihoods: An Urban Application to Turkish Gecekondu Households. International Journal of Urban and Regional Research, 37: 769–789. doi: 10.1111/j.1468-2427.2013.01205.x
Publication History
- Issue online: 26 FEB 2013
- Version of Record online: 19 FEB 2013
- Abstract
- Article
- References
- Cited By
- coping;
- household;
- livelihoods;
- poverty;
- resource profile approach;
- strategy;
- survival;
- Turkey
This article critically examines the existing conceptualizations of and explanations for the socioeconomic behaviour of poor households in order to lay the foundations of a new model designed to extend the existing resource-based approach to livelihoods. The proposed model groups 'household responses to poverty' into four key types: income generation, income allocation, consumption and investment. In explaining household responses and their poverty outcomes, it focuses on the role of different resources beyond income (e.g. social capital), along with the wider structural forces and household characteristics that influence the availability and benefit delivery capacity of these resources. The new model is shown to provide a theoretically more sophisticated framework with greater explanatory power and empirical applicability.


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Originally posted on Phillies Nation | Last updated 6/18/14
-Good news this week for Larry Greene Jr., who was previously said to have required surgery to repair his ailing left wrist. The 21-year-old outfielder has resumed game action after spending time in a brace and is playing intrasquad games with the group that is slated to become the Gulf Coast League Phillies. The Phillies' top draft pick from 2011 anticipates that he could be activated for the Class A BlueClaws by July 1st. Greene's original diagnosis was a cartilage tear. Prior to being sidelined, the Georgia native posted a .167 average with five RBI and two steals in 15 games with Lakewood this year. The GCL kicks off its season this coming Friday. Greene could continue action there once their season begins. -Two other outfielders made their returns for the Double-A Reading Fightins on Tuesday. Former 1st round draft selection Zach Collier (back) and 2009 second round pick Kelly Dugan (oblique) were in the lineup, going 2-for-4 and 1-for-4 respectively. The 23-year-old Collier, who drove in two runs in his return, sports a .214/.308/.282 slash line in 34 games this season. Dugan, 23, has posted a .275/.396/.375 slash line in 14 games for Reading this year. Collier and Dugan are each on the Phillies' 40-man roster. -In the Class A South Atlantic League All-Star Game, the contest finished in a 4-4 tie after 10 innings. The game took place at the home of the Rangers affiliate Crawdads in Hickory, NC. Four Lakewood BlueClaws players saw action in the event… Lefty reliever Cody Forsythe threw a scoreless frame. Shortstop J.P. Crawford went 0-for-4 with a walk. Outfielder Samuel Hiciano went 1-for-3 with a double. Catcher/first baseman/DH Willians Astudillo went 1-for-5 as the North division's designated hitter. -For the short-season A level Williamsport Crosscutters, outfielder Jiandido Tromp collected three hits, including two home runs in a 12-5 win over Jamestown on Tuesday. The 20-year-old Aruba native is 5-for-15 (.333 avg) through four games with the Cutters. The righty batting Tromp was an All-Star for Williamsport last season, when he batted .299 with a homer and eight RBI through 33 games prior to being promoted to Lakewood. He tallied a .224 average with a home run and nine RBI in 27 games with the BlueClaws earlier this season.
PLAYERS: Zach Collier, Kelly Dugan
TEAMS: Philadelphia Phillies
TEAMS: Philadelphia Phillies
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East Lyme - Parents worried about mixing high school and elementary students in the same building raised concerns Monday about running the Coastal Connections high school program out of Niantic Center School.
The program, which includes about 25 high school students, calls for them to attend classes three days a week and have internships the other two days, according to Program Director Mike Sullivan. It is currently located in a Flanders Road building that houses a children's day care center, a dentist and special education program for students 18 to 21.
In a presentation to Niantic Center School parents, Coastal Connections students spoke about their internships and future plans, while administrators showed how the two groups of students would be in distinct areas of the building with separate entrances.
During the meeting, which was attended by about 50 people, some parents questioned the security of the proposal. There were questions about how the doors between the two sections would be locked and if students would interact with each other.
The proposal is part of an effort to cut rental costs, as well as other savings in oil and transportation, to preserve the student programs and not lay off teachers in light of a $650,000 cut in the proposed school budget, explained Superintendent of Schools James Lombardo.
Lombardo said moving the program to Niantic Center School would save at least $12,000. Some parents said it would be less.
Coastal Connection is also looking for a new home because the special education program for 18-to-21-year-olds, which is now housed in the same building as Coastal Connections, would need more space next year as more students enter the program.
Lombardo addressed the fact that there was some misinformation about the Coastal Connections program such as that it includes expelled students. He said the high school students would have different schedules than the elementary school students.
One Coastal Connections parent said that the high school students understand real-world behavior and work in a variety of settings, such as volunteering at charities.
"I think your kids will benefit from our kids being here," said John Leonard, whose daughter attends the program.
But parents emphasized that it was not the quality of the students or programs they were concerned about, but the mixing of any high school students with younger students, as well as fears after the Newtown tragedy.
One resident, Maureen Hahn, suggested the alternative of bringing the fifth-graders back to the elementary schools and then using the middle school space for the high school program, which would be "much more age appropriate."
Lombardo said he would reflect on what was said as the meeting with other administrators before deciding whether or not to make a recommendation to the board next week.
East Lyme won't relocate high school program to elementary school
Analysis: Get ready for the nastiest, most unpredictable prsidential campaign you can imagine
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14 Parks near Apple Valley, Minnesota
Rosemount, Minnesota 3.89 miles E
Burnsville, Minnesota 4.13 miles NW
Eagan, Minnesota 4.94 miles NE
Lakeville, Minnesota 6.37 miles SW
Farmington, Minnesota 7.39 miles SE
12100 Johnny Cake Ridge Road Apple Valley, Minnesota 55124 (map) | (651) 480-7773
Sites: 93 | Latest Rate: $35.00 | 77 Reviews
|Clean Restrooms:
|Clean Showers:
Jul 2016 - $35.00
This county-owned park is neat and clean to a fault. An employee politely knocked on our door when a guest parked on the grass. The two large pull-thrus (56 & 57) are isolated from the other sites. There is some aircraft noise, not bad in a motorhome. Recycling is extreme: campers are issued color-coded bags for trash, recycles and a separate one for composting. Wi-Fi was solid. There is a super grocery store - HyVee - a couple miles south. Minneapolis is to the north and an easy drive. Bicycle rides around the Minneapolis city lakes revealed fabulous houses. Restaurants and bicycle rentals are available at the lakes. - Mtmoi
Jun 2016 - $28.00
Really enjoyed the site due to the semi-seclusion. Was quiet and had lakes to swim, kayak and hiking. Mountain biking is very near campground. Would definitely camp here again. - kaseyA
Jun 2016 - $35.00
Nice enough park, would not consider it a campground. Sites pretty close together. Crazy narrow, winding entrance way. Hope you do not meet another vehicle. Wifi worked pretty well. Water bib at front of site, may require extra hose. Sites fairly level. In a nice area of town but setting inside park seems more rural. A lot of stations over the air, Verizon worked well. - rockhill
Farmington, Minnesota (map) | (651) 463-8818
Sites: 100 | Latest Rate: $20.00 | 5 Reviews
|Clean Restrooms:
|Clean Showers:
Jul 2016 - $20.00
Paid for a month at $400. Will leave on 8/3 due to the fair. We can come back to use the remainder of the 30 days. The campground closes in the middle of September. Maintenance is very good. Nice grass kept up by maintenance. Mower available to trim around your site. Tables available upon request. If Host not available when you enter, just pick a spot and set the rear of the coach in line with the utilities. - easydoesit
Jul 2015 - $20.00
This campground is about 30 minutes south of Minneapolis. It's pure fairgrounds camping: a big, mostly level grassy area with no trees to speak of and just the basics for a RV. There are no sewer hookups but there's water and 50 amp electric and a nearby dump station. The camping area is set up for clusters of four RVs to set up around four hookup power/water pedestals. That's not immediately apparent upon arrival, though, because there are a few exceptions to that setup (along the roads) and also, some folks park a distance away from their hookup point and stretch cords to their hookups, giving them some elbow room from their neighbors. There's a range of people in the campground - guys working in the area, retired people, and families all taking advantage of probably the lowest camping rates in the Twin Cities area. The fairgrounds has lots of good gravel roads, so there's plenty of places for a nice walk. There are restrooms (although the one right at the campground was undergoing repairs during our stay). I saw a single shower in the restroom, though, and it didn't look very inviting - the toilets, though, were acceptably clean. We had full scale Verizon 4G and, with no trees to speak of, no problem getting a satellite signal. The county fair takes place in August, during that time all campers have to be out, as the area is used for vendors and parking. - nazpaz
Jun 2015 - $42.00
Clean park, level sites. Did not use any of the amenities as this was a one night stay - moving on to Iowa. - Jim MacIsaac
Savage, Minnesota (map) | (952) 445-1756
Sites: 80 | Latest Rate: $40.00 | 37 Reviews
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Jun 2016 - $40.00
We booked in advance and paid when we arrived for full hookup. We were then directed to our site. It was a corner site and the 5th wheel next to it was huge; they had two pickups and a large trailer on the site which they had to move before we could even get down the row. In the corner (and not on their map) was an old run-down trailer with a large wooden deck that had holes in it. The man guiding us said someone lived there (didn't look like it). After looking at the space that had low tree branches that were about 10 feet off the ground we said we couldn't park there. According to the office that was the only full hookup left so we were directed to a better site with no sewer. We did get a partial refund. When I mentioned the rundown trailer the lady said no one lived there so not sure which it was; vacant or occupied. Either way it was not somewhere you'd want to be next to. TV reception was good. Site was clean and level but right in front and across from the dump site so lots of traffic. After the hassle of pulling in, which included waiting for two people to move cars out of the site we were supposed to go in, I went to the ladies' shower and there was a sign on the door that read "Men's restroom closed Sunday night to Monday so this restroom is co-ed". Obviously I went back to our trailer to shower. A hot tub was also advertised but was not working; we were told it hadn't worked for a month. This should have been disclosed when we booked it. Could be a nice park if attention to detail was done. - Catsinatrailer
Aug 2015 - $35.00
Clean restrooms-granite countertops with bronze fixtures, wow!
Great staff so polite and helpful. If ever I am in the Minneapolis St. Paul area I will stay there again. Quiet place. Nice pool and jacuzzi. Had to pay extra for a pull thru but, level and fresh gravel. - starcraft Travelers
Jul 2015 - $42.00
Towne and Country Campground, Savage MN. This is an RV and travel trailer campground, not really optimized for tenting, but there are several family tenters here. We stayed in sites 19, 23 and 74. Sites are close, but good foliage makes them seem more separated. Full amenities, very close to Minneapolis. Full, modern shopping one mile south in Savage, Minnesota. Most of their RV sites are level with mature shade trees. Clean, well maintained, family atmosphere. Staff are friendly and help you back your trailer into your site. Showers and latrines are immaculate. Two washers, two big driers (quarters only). Small camp store in the office sells necessities. Surprise free random ice cream social in the game room on one day of our six-day stay! Rented a fire pit with wood bundle for only $5. Just added new sand to kids' playground and upgraded the Internet connection. Dump site turn-out is close to the entrance-exit. Highly recommended. - Dick and Linda
Prior Lake, Minnesota (map) | (952) 445-8800
Sites: 122 | Latest Rate: $30.00 | 108 Reviews
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Jul 2016 - $30.00
The $30.00 rate is based on a 7 day stay weekly rate.
I see that several people hace left reviews recently, so all I can do is to echo the same as they have said. This is a beautiful well manicured and kept park. The casino complex rivals anything in Las Vegas, and Hank Williams Jr. played the week we were there. The full sized bus to the Mall of America is great. 22 miles away, takes about 30-40 minutes. The gym complex is beautiful, about 1/2 mile away with the local shuttle service available if you want and is yours for $5 per day. Local shopping is about 3-5 miles in any direction for food etc.
As with all Tribal owned campgrounds, there is never any cable tv connection, as they want you in the casino, not watching tv. However, being 25 miles SW of Minneapolis, we were able to pick up numerous (34) stations over the air with our King digital antenna.
The only down side we did not care for was that 2 sites are always paired together, with both sets of utility connections sharing the same center island area, so that when you pull in and connect, your neighbor must pull in the opposite direction to connect. Result is that your rv's are about 5-8 feet apart back to back. So if you both have big slides, you can almost open your windows and shake hands with your neighbor! The front of your site is open and grassy and a reasonable distance to the next rv. Overall, a very nice place, reasonable priced with the best on site fuel price around. - AlaskaJack
Jun 2016 - $39.00
I would stay at this park even if I wasn't just passing through across country. Super, super clean. Great customer service. They have free shuttles all over the property. We stayed here because of the free, yes free, shuttle into the Mall of America. They have shuttles that will take you all over the area. Seriously this is a great deal!
The sites are level, wide and well kept. The park is beautiful and the casino is nice too. They have cheap fuel on site and an RV wash too. Just a beautiful property.
There is no "clubhouse" per se but you can pay $5 per person to gain access to their fitness center.
The bad - The wifi here is not good. I think that is the only bad thing I can say about this park. - scruggsfamilyRV
Jun 2016 - $35.00
Sites are paved and level but a little close to one another. The park is clean and quiet. The Wi-Fi is horrible and we could not get it to work during the 5 nights we were there. Security made regular rounds through the park. They have their own fuel island on site and the price is as good as anywhere in close proximity. I would rate the park a 9 if the Wi-Fi worked. - cwousa
Shakopee, Minnesota (map) | (952) 445-7313
Sites: 108 | Latest Rate: $34.00 | 12 Reviews
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Sep 2012 - $34.00
From the pictures and description on the website, we had high hopes for this campground. Upon arrival, we were put in a campsite where the hookups for the water and electric were broken. So we had to move to a different site, after we had already unhooked and setup. The part of the campsite closest to the river resembles a gypsy camp. There are various makeshift tents constructed of tarps and chicken wire. There are loose dogs running around. Broken down cars covered with tarps. The bathrooms and showers are infested with spiders. The stall doors have so much rust on them that the bottoms are falling off. The toilet paper was always empty in a least one of the stalls. In the stalls that did have paper, the toilets were plugged. The pool looked as if it had not been cleaned for a very long time. There were cars racing in and out of the campground at all hours of the day and night. I would not recommend this campground to anyone, let alone campers with small children, as they would not be safe. It's really unfortunate that this campground is not properly maintained, as it could be quite beautiful and it is in a superb location. Needless to say, my family and I will not be staying at Shakopee RV park again. - MNCampingFamily
Aug 2011 - $12.00
Everything was subpar. Starting with being quoted three different rates for camping by an employee, to being told conflicting information as to sites available. Our second day we had to move to a new site due to our campsite being used as a bike ramp and social drinking area. We were told we would have electric, but there was no access from the tent areas. Loose dogs were in and out of our campsite: leaving waste in our site the owner did not attend to. The park seemed to think the only issue was noise of dogs but we had issues with the shower house water temperatures being too hot or lukewarm, the pool was not being heated, the bathroom and shower house doors did not always shut or lock due to rust. We were so dissatisfied we chose another campground to go to. The owner was unpleasant and tried to change our nightly rate to say "we owed him" when his sign on the wall said "two persons/1 tent= $300/month." We stayed a month, were okay with paying for the month but wanted the $300 back for the month we weren't staying. He tried to tell us that you couldn't take apart the payment to get a refund at all for canceling. Then at the mention of a lawyer and the Better Business Bureau, he handed me two hundred and said, "There, a good compromise, look forward to having you back next year." Seriously? There are many other campgrounds in the area. I have found many nicer and more professionally run choices. I will not be staying here again. - gypsysojourner
Jul 2011 - $40.00
When we arrived, the entry area was so full of vehicles, you couldn't pull an RV in there. So we parked the RV at the nearby restaurant. After running the gauntlet of smokers outside the office door, we were told our site wasn't available, but they would give us a different site (with sewer) at no extra charge. A "really nice" site. Not very welcoming or friendly. The road to the site was horribly pot-holed. The roads are very narrow, and one parked RV had his awning out into the road. The site was extremely unlevel and muddy. When we got to the site, we saw why our original one wasn't available; 75% of the sites are flooded! It's on the Minnesota river, and it was apparent that most of the sites had been flooded at one point. There was very little gravel to park on and very little "grass" to walk on. Parking the towed vehicle was a challenge. While we were here it rained even more, and the water got to within 10 or 15 feet of our rig. This reservation was made in April, and no attempt was made to contact us to let us know the situation at the campground, nor was anything said at the time of checkin. Overall, what sites were available were very narrow, very run down looking, very damp due to the heavy tree cover. We would not stay here again. There are other options within the Minneapolis/St Paul area. - cobragt23
Jordan, Minnesota (map) | (952) 492-6440
Sites: 111 | Latest Rate: $40.00 | 18 Reviews
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Jun 2016 - $40.00
Nice office staff, stay only if you can get one of the deluxe sites, they are very nice. Our site was very small and could not believe they called it a pull thru. Sites are packed together on any piece of ground there. Okay for a night or two if you want to visit the Mall Of America. No cable and it`s hit or miss on getting TV . - ottosprings
Aug 2015 - $49.00
Amazingly, the bugs were not bad at all...because this is a heavily wooded campground. Satellite reception? Not likely. The Internet was good. Cellphone reception is also, very good. This campground is under new ownership, and needs allot of help. I would think that Minneapolis could support a great KOA. On the bad side: the dust was bad, the workers were not very friendly, the roads were in some cases overly narrow, and there are no planned activities. I was disappointed. We will not likely return. - sse
Jul 2015 - $24.00
Under new ownership. The roads are too narrow for big rigs to get through and are 2-way. Right outside the front gate are 2 heavily used trucking companies which leaves everything outside your rigs covered in dust. Staff is unfriendly, sites are un-level and internet turns off every night around 8:15. Waiting for a spot to open at the nearby casino so we can leave. - Bthemockingjay
2501 Lowry Ave. NE Minneapolis, Minnesota 55418 (map) | (612) 781-3148
Sites: 30 | Latest Rate: $53.00 | 7 Reviews
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Aug 2015 - $53.00
This park needs some serious work. Spaces designated for RVs are fairly haphazard. We plugged into an electric box that already had at least one RV plugged in with other cords coming out besides. Spaces very close to each other with very little room for parking a vehicle. Woke up every morning at 5:30 a.m. to the neighbor talking loudly/yelling to her (five--yes, FIVE!!) pitbulls while allowing them to relieve themselves behind our motor home and never once cleaning up after them. Bathrooms were scary--not private at all. Shower curtains hide the stalls with no doors on the bathrooms themselves. My husband went in the first morning to find the stalls in the men's bathroom covered in vomit. Park itself is in the great neighborhood of St. Anthony but inside the park is a different story. Very run down. Manager nice and does what he can but owners should hire more help! A few rules regarding age of units and pet restrictions would clean up this park in a hurry. Ridiculously overpriced considering we couldn't use the facilities at all. We only used the park for sleeping--didn't use bathrooms, laundry, etc. - desertrat74
Jul 2015 - $32.00
Approximately 60% of the spaces are fulltime, low income residents. Though the majority are nice people, there are a few unsavory characters. The manager is a "Jack of all trades". He is a wonderful, caring person...but stretched between this and 2 other sites. Access to the site was acceptable. the original site they put us in did not allow us to extend our awning as we were literally 4 feet from campers on either side. We moved to another site, that allowed use of the awning and was approximately 20' from the unit next store.
We chose this facility because of its proximity to downtown Minneapolis and the fact that the public transportation stopped right outside the park. (We do not tow, so access to public transportation in an urban environment is a real plus. That and reliable, accessible power and water were the only positives! - Ncw
Oct 2014 - $38.00
Many permanents, which creates noise in the AM when they leave for work. Some units have a bit of junk around them. The park office closes mid-afternoon and after that the manager must be called. He apparently has another full-time job but is very helpful and cooperative. Utilities were good. This is not a destination resort but should serve very well for a day or week or more. This is a very urban setting for a park but it is close to the center of town. We felt quite safe here and would definitely stay here again because of it's central location. - gene a
Hastings, Minnesota (map) | (651) 437-5269
Sites: 85 | 0 Reviews
Cannon Falls, Minnesota (map) | (507) 263-4447
Sites: 35 | Latest Rate: $30.00 | 8 Reviews
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Jun 2013 - $30.00
You are a bit close to other campers and if they are the barking dog or screaming kids people it will be like they are in your campsite. They do not allow mats, which we found out when we received the 'warning' from the office folks. I can understand, they have very nice grass at the sites. Pads are gravel and level. One thing we noticed is that there is no where walk. There is no sidewalk or path to walk on. You walk on the road which is very narrow. Not a huge deal but noticeable. If you want to sit around the fire ring you are literally right next to your neighbor. Not much privacy. The town of Cannon Falls is very close and a fun place to spend a little time in. Overall nice and a decent place to stay. - LP2013
Jun 2010 - $35.00
Campground was family friendly for it had activities for kids. There was a lot of noise from the road where we were parked. The lake was getting green so swimming was not an option. The staff were helpful. - happycamper100
Jun 2010 - $25.00
This is a very nice park that is on a very nice lake. The sites are all back in sites. They all have a good view of the lake. There is a very large and nice playground. The bathrooms are very nice and clean. The east side sites have more shade than the west ones do. Very nice park. Well maintained. We will be back. - PackerFanRick
Hastings, Minnesota (map) | (651) 430-8240
Sites: 80 | Latest Rate: $30.00 | 10 Reviews
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Jul 2016 - $30.00
What a gorgeous park. The sites are large and the pull through sites have water. We will be back. - grdngrl
Jun 2016 - $35.00
This is a large, well kept county run campground. Very comparable to many COE campgrounds we have stayed at. This is one of our favorite places for a quick local getaway, but there are some idiosyncrasies to the place that let you know the people in charge may not be in touch with the modern RV experience.
On our most recent visit we had a pull through that was very steep front to back. Once unhooked, in order to level our trailer the tongue was almost on the ground. Other sites have posts that mark each campsite placed precariously close to the pad, making backing or pulling into your spaces extremely difficult. And finally, they have a strict "no dog" policy for the campground, but dogs are welcome throughout the rest of the park and hiking trails. On this particular visit we felt the park host was somewhat overzealous in his enforcement of rules. On a midweek night, with the park virtually empty and not another camper within several hundred feet we were told our quiet campfire conversation was disturbing other guests. The next morning I was chastised for not having a paper tag with our check out date attached to our campsite marker. I had never received one, and was asked to stop what I was doing and drive to the front gate and obtain one. Once there, the same teenager that checked me in admitted that she forgets to give them out from time to time.
These things aside, it really is a wonderful campground located within a beautiful regional park. There are several miles of hiking trails, a modern boat landing, playgrounds, picnic shelters and other typical park amenities. - scott1k
Jul 2015 - $25.00
Extremely large and neat sites all pull through in the modern campground area. Electric and Water only but very clean dump station, Site Z is on the corner looking into woods and field and we regularly saw deer walking through. There is a beach and boat access, along with conference centers, a playground, volley ball court, tennis court, and many other common areas. NO PETS are allowed in the campground (although we saw them in the boat dock area). It was largely empty the entire time we were there and the fellow campers were quiet and polite. My largest complaint was the office staff and campground hosts. They were not very friendly to "out-of towners" and complete sticklers for the rules. That being said, aesthetically it was a beautiful park, one of the nicest we have stayed in. There is no wifi, but my ATT coverage was good. The price is $25 a day and what is not very clear on their website is there is an additional per car $5 day access pass you have to pay for on arrival. (Reservations for the campground are done online.) The annual pass is $25 which you can purchase if your stay is 5 days or longer. They are also inflexible with their cancellation policy. We left a day early and even though we told them that at the beginning of our one week stay they were unwilling to refund us that day. You can stay in the park for one week but then need to move to another spot if you are going to stay longer. - Lee and Trace


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- Member since Dec 22, 2002
Monica Sanowar
Families researching:
Recent Activity
- Monica became a member of AncientFaces. Dec 22, 2002
- Monica added the photo Alethea Preston Pinn, VA Jun 18, 2012
- Monica added the photo Flora Virginia (Jones) Wood, VA Jun 19, 2012
Monica's Posts
Monica Sanowar 3 Cans drained white shoe peg corn pinch of nutmeg pinch of cinnamon pinch of salt 1/2 cup sugar 1 pint whipping cream 1 can Eagle Brand condensed milk 4 Eggs beaten 1 tablespoon vanilla extract 1/4 stick of butter Try to get all the excess water from the corn. In a saucepan, heat condensed milk and whipping cream and butter together. Add in the beaten eggs and whip it. Do not boil. Take off the heat and pour the mixture over the corn and add the sugar. Beat it a little more. Oven should be preheated to 425 degrees. Set glass bowl into a baking pan and fill the pan halfway up with water. Sprinkle the nutmeg, and cinnamon on the top. Cook for about 45 minutes or until you stick a knife into the center and it comes back clean. Should be a light golden brown around the edges. Enjoy!
Dec 01, 2002 · posted to the surname Jones
Monica Sanowar Whoever she was, she was absolutely beautiful. You can tell her folks had means, look at that beautiful dress.
Jul 25, 2012 · posted to the photo Gassagne girl?
Monica Sanowar Morning Alex! I had not really been on this site in some years. It was not EASY changing that picture, I kept getting these annoying pop-ups. You were not the 1st to realize that that dress was way past Molly's age. I think her name was Margaret, but I will check. Will send you an email on the rest.
Jun 16, 2012 · posted to the photo Alethea Preston (Pinn) Colvin, Virginia
Monica Sanowar Aunt Elizabeth said she was 15 when this picture was taken.
Jun 15, 2012 · posted to the photo Elizabeth Colvin,Washington D.C. 1915
Monica Sanowar She was Mary Elizabeth but she was never called Mary.
Jun 14, 2012 · posted to the photo Dorothy Colvin, Virginia
Monica Sanowar When we first developed this picture about 10 years or more ago, we thought this was Molly. This is actually a picture of ALETHEA PRESTON PINN.
Jun 14, 2012 · posted to the photo Alethea Preston (Pinn) Colvin, Virginia
Monica Sanowar Aunt Dot and Aunt Elizabeth were the daughters of GEORGE COLVIN and MAMIE FREEMAN. GEORGE COLVIN was the son of JAMES (JIM) COLVIN and ALETHEA PRESTON PINN. When James died, Mama Kate (Alethea's daughter) went to live with she and her husband Murray Tapscott. Hope that clears it up.
Jun 14, 2012 · posted to the photo Dorothy Colvin, Virginia


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Phoenix Suns
Report: Marcin Gortat's trade value may have taken a hit
With the NBA trade deadline approaching Thursday, Suns center Marcin Gortat was thought to be a hot commodity on the market.
But according to ESPN Insider, Gortat's trade value may have taken a hit.
Over the last three games, he's managed to score just 2, 6 and 4 points and two of those games came against an Oklahoma City team that potentially may have been one of his biggest suitors. He also hasn't been the defensive force or shot-blocker that he was at the start of the season.
The 29-year-old has averaged 11.3 points, 8.7 rebounds and 1.7 blocks per game this season.
Since the Suns' misfortunes this year have forced them to turn their attention to rebuilding for next season, Gortat was thought to be expendable.
But, the Suns may opt to keep Gortat if they are unable to find a deal to their liking.
Most Popular
Suns Audio
Vinny Joe Trivia - Amar'e Stoudemire
Thursday July 28
Vince takes on AZCentral Suns reporter Paul Coro in an Amar'e quiz full of controversy
Paul Coro, AZCentral Suns reporter
Thursday July 28
Coro talks Amar'e retiring a Knick and previews the upcoming Suns season.
Alan Hahn, ESPN New York Radio Host
Wednesday July 27
Alan Hahn discusses why Amare Stoudemire retired as a Knick rather than a Sun?
Yay or Nay?
Wednesday July 27
Amar'e should be in the Suns Ring of Honor, Dave Coulier was funniest on Full House + more
Frank Isola, NY Daily News NBA reporter
Wednesday July 27
Isola talks about why Amar'e chose to retire with the New York Knicks.


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*holiday apartments outside of hotels or B&Bs mostly offer a delivery service of freshly baked rolls.
If you have any questions about our accomodation catagories, please get in touch with us via the contact form. To the contact form
Offering accommodation to guests, which is not part of a package deal, then Sächsische Staatsbäder GmbH is only a contact link between guests and host – owning the accommodation.


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Trans Youth Face Higher Risk Of Abuse, Mental Health Problems If Not Affirmed
Two new studies on transgender and gender nonconforming youth have been published in last month's volume of Pediatrics that provide further evidence that young people need to be accepted and affirmed for their identities. Not only do they face severe mental health consequences from stigma, but they are at higher risk for family abuse as well.
The first study (full article) found that young people who experience gender dysphoria but cannot access treatment face higher rates of psychiatric problems. Many of the kids in this study (21.6 percent) already had a history of self-mutilation or attempted suicide before seeking treatment, but helping them achieve congruence between mind and body alleviated the mental health burden. The study recommended that doctors and counselors work with families to affirm gender variation so that it does not become a source of internal conflict for the transgender child.
This approach is not without its own challenges, as the second study (full article) found that stigma against gender variation is often too close to home. In fact, gender nonconformity is a high risk factor for children to be sexually, physically, or psychologically abused, and that abuse can lead to a lifetime of post-traumatic stress disorder that often goes untreated. The abuse can reflect parents' discomfort with gender nonconformity, their homophobia, or a sense that their own parenting is to blame.
An accompanying editorial highlights the fact that not all young people who question or explore their gender are truly transgender, but the available research indicates the importance of affirming that exploration and assessing potential challenges the child might face:
The pediatrician or family medicine doctor should be on the lookout for the child who is gender nonconforming… The pediatrician who observes gender nonconformity should address the issue straightforwardly and look for a number of associated psychosocial problems including abuse, PTSD, difficulty in school, depression, or increased anxiety. Referral to and working with the mental health professional provides a good safety net for the child as he/she struggles with exploration of gender orientation, gender, and gender role as well as the related conditions. If indicated, adolescent patients might be referred to a pediatric endocrinologist for help in getting a better long-term physical outcome.
Though conservatives consistently object to any discussion of LGBT issues with young people, it seems it is young people and their families who need those conversations most.


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PlayStation Optimus Prime looks awesome
Here's some photos of the PlayStation Optimus Prime in all its glory.
We showed you a few diagrams the other week, but here's the PSone/Transformers mash-up in real life.
And as a bonus, here's the Megadrive Megatron.
Thanks to Radiokaikan for the photos. Hit up your local importer for price and launch details.
Sometimes we include links to online retail stores. If you click on one and make a purchase we may receive a small commission. For more information, go here.


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Dogfish Head El Diablo Verde(RETIRED)
RATINGS: 1 MEAN: 4.1/5.0 WEIGHTED AVG: 2.94/5 SEASONAL: Special IBU: 70 EST. CALORIES: 246 ABV: 8.2%
El Diablo Verde is the first beer from our co-worker Small-Batch Brewing Program to make it to the taps of the brewpub. This program encourages any Dogfish Head co-worker with an off-centered brew idea to team up with a couple co-workers and create their beer on our 10 gallon Sabco Brew-Magic system at the brewery in Milton. (click here for a story on the program and the beer!) These beers are then informally judged by all co-workers during our weekly Beer:30 on Friday afternoons. The highest scoring brew from each quarter then moves on to have their beer scaled up at the brewpub. El Diablo was the winner for the first round of brews, which were all made in the last quarter of 2011, and was brought to life by Lou Carrazzone and Ryan Harvey, both brewers in Milton. As the name suggests The Green Devil is a hoppy double IPA brewed with heaping amounts of jalapeno pepper and cilantro. The aroma is full of jalapeno twang and a grassy green brightness intermingled with citrusy hops. Jalapeno hits the taste buds first with heat up front and a delicious smack of hops with a malty middle and bitter finish. Undoubtedly the quintessential pairing for our Fish Tacos.
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